Dissociation constants, spectrophotometric determination

The acid dissociation constant of the free ligand, when the proton attached to the nitrogen dissociates, is approximately 10 14 B, and the effect of metal chelation is to increase this dissociation constant by a factor of 10B to 108. The values of Ka, and Ka the stepwise dissociation constants, were determined spectrophotometrically and potentiometrically, and the acid-strengthening effect on the NH group was found to depend markedly on the chelated metal ion (95). The order of increasing acidity is Mn(II) < Cd(II) < Zn(II) < Ni(II) < Fe(II). The values of pKa, and pKat for any one metal were found to be within 1.3. It therefore appears that these... 

SPECTROPHOTOMETRIC DETERMINATION OF THE pAT VALUE OF AN INDICATOR (THE ACID DISSOCIATION CONSTANT OF METHYL RED)... 

Discussion. The dissociation of an acid-base indicator is well suited to spectrophotometric study the procedure involved will be illustrated by the determination of the acid dissociation constant of methyl red (MR). The acidic (HMR) and basic (MR-) forms of methyl red are shown below. 

Spectrophotometric determination of the pK value of an indicator (the acid dissociation constant of methyl red) 718... 

Tam, K. Y., Takacs-Novak, K. Multiwavelength spectrophotometric determination of add dissociation constants. Part 11. First derivative versus target fador analysis. Pharm. Res. 1999, 16, 374-381. 

In this way Kolthoff and Bruckenstein59 determined spectrophotometrically at 25° C for acid-base equilibria in glacial acetic acid the following ionization and dissociation constants of the bases ... 

Mitchell, R. C. Salter, C. J. Tam, K. Y., Multiwavelength spectrophotometric determination of acid dissociation constants. Part III. Resolution of multi-protic ionization systems, J. Pharm. Biomed. Anal. 20, 289-295 (1999). 

In a series of papers (Cohen and Lach, 1963 Lach and Cohen, 1963 Lach and Chin, 1964a,b Pauli and Lach, 1965 Lach and Pauli, 1966), Lach and co-workers used a similar technique to evaluate the effect of the cycloamyloses on the solubilities of a variety of pharmaceuticals. Plots of the solubility of the pharmaceutical against the concentration of added cycloamylose were usually linear with slopes ranging from 0 to 2.25. In theory, these slopes can be related to the dissociation constants for the cycloamylose-substrate complexes if the stoichiometries of the complexes can be determined (Thoma and Stewart, 1965). This technique, however, is inferior to the spectrophotometric method to be discussed presently. 

By correlating the observed spectral changes with the concentrations of added cycloamylose, dissociation constants of the cycloamylose-substrate adducts may be calculated (Rossotti and Rossotti, 1961). Values of the dissociation constants determined in this manner for a variety of complexes are presented in Table II. In most cases, stoichiometries of the complexes have been shown to be 1 1 from the presence of distinct isosbestic points in the spectrophotometric titrations. In a few cases, additional spectral perturbations are observed as the cycloamylose concentration is increased, indicating more complex modes of association. Methyl orange, for example,... 

The proton dissociation constants, of two series of 3,7-bis(arylazo)-2,6-diphenyl-1 //-irnidazo[l,2-7]pyrazoles, in the ground state and the excited state were determined by the spectrophotometric method and utilizing the Forster energy cycle, respectively. These constants were correlated by the Hammett equation and the results of such correlations with spectral data indicated that both series of compounds exist in solution almost exclusively in the l//-bis-(arylazo) tautomeric form A <2002T2875> (Scheme 3). 

Drug dissociation constants are experimentally determined by manual or automated potentiometric titration or by spectrophotometric methods.40 Current methods allow determination of pXa values with drug concentrations as low as 10 to 100 pM. For highly insoluble compounds (concentration <1 to 10 pM), the Yesuda-Shedlovsky method41 is commonly used where organic cosolvents (i.e., methanol) are employed to improve solubility. The method takes three or more titrations at different cosolvent concentrations, and the result is then extrapolated to pure aqueous system. The dissociation constant can also be determined with less accuracy from the pH-solubility profile using the following modification of Henderson-Hasselbach equation ... 

Cessna, A.J. and Grover, R. Spectrophotometric determination of dissociation constants of selected acidic herbicides, J. Agric. Food Chem., 26(l) 289-292, 1978. 

The benzhydryl chlorides and BC13 react with formation of ion pairs (ionization constant, Ki) which dissociate to give the free ions (dissociation constant, KD). Because paired and free diarylcarbenium ions show only slightly different UV-visible spectra, [41], spectrophotometric measurements allow the determination of the total carbocation concentration. On the other hand, only free ions are detected by conductometric analysis, and a combination of both methods allows the determination of Ki and Kd using the theory of binary ionogenic equilibria [42,43]. 

Dissociation constants of ionizable components can be determined using various methods such as potentiometric titrations [85] CE, NMR, [86] and UV spectrophotometric methods [87]. Potentiometric methods have been used in aqueous and hydro-organic systems however, these methods usually require a large quantity of pure compound and solubility could be a problem. Potentiometric methods are not selective because if the ionizable impurities in an impure sample of the analyte have a pK similar to that of the analyte, this could interfere with determining the titration endpoint. If the titration endpoint is confounded, then these may lead to erroneous values for the target analyte pKa. 

The electrophoretic mobility of a neutral base B in a buffer at a given pH is correlated to its thermodynamic dissociation constant. Such correlations were used for determination of the pKd of HAA belonging to classes B and C of Table 2, by CZE-UVD (at 214 nm) of these compounds in buffers of pH from 3 to 9. The pKd values obtained by the CZE method are the same as those obtained from UW spectrophotometric measurements256. The pKd values derived from these experimental measurements are different from those appearing in Table 2, because the latter values are purely calculated ones (see note a in the table). 

Ross and Riley (11) determined the macroscopic dissociation constants for lomefloxacin using UV spectrophotometric measurements at 266 nm. Takacs-Novak et al. used UV spectrophotometry to determine octanol/water partition coefficients for lomefloxacin and related quinolones and related them to their protonation equilibria (18). 

Tam, K.Y. and Takacs-Novak, K. (2001) Multiwavelength spectrophotometric determination of acid dissociation constants a validation study. Analytica Chimica Acta, 434, 157—167. 

Roman L, Mirel S, Plorean E, Oprean R. The potentiometric and spectrophotometric determination of dissociation constants for same 2-mercapto-5-R-amino-l,3,4-thiadiazole derivatives. J Pharm Biomed Anal 1998 Oct 18(1-2) 137-144. 

Takacs-Novak K, Tam KY. Multiwavelength spectrophotometric determination of acid dissociation constants part V microconstants and tautomeric ratios of diprotic amphoteric drugs. J Pharm Biomed Anal 2000 Jan 21(6) 1171-1182. 

Tam KY, Takacs-Novak K. Multiwavelength spectrophotometric determination of acid dissociation constants Part II. First derivative vs. target factor analysis. Pharm Res 1999 Mar 16(3) 374-381. 

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